Publications by authors named "Maryam Mukhtar"

31 Publications

Predictors of Permanent Pacemaker Implantation in Patients Undergoing Transcatheter Aortic Valve Replacement - A Systematic Review and Meta-Analysis.

J Am Heart Assoc 2021 Jul 14;10(14):e020906. Epub 2021 Jul 14.

Thomas Jefferson University Hospitals Philadelphia PA.

Background As transcatheter aortic valve replacement (TAVR) technology expands to healthy and lower-risk populations, the burden and predictors of procedure-related complications including the need for permanent pacemaker (PPM) implantation needs to be identified. Methods and Results Digital databases were systematically searched to identify studies reporting the incidence of PPM implantation after TAVR. A random- and fixed-effects model was used to calculate unadjusted odds ratios (OR) for all predictors. A total of 78 studies, recruiting 31 261 patients were included in the final analysis. Overall, 6212 patients required a PPM, with a mean of 18.9% PPM per study and net rate ranging from 0.16% to 51%. The pooled estimates on a random-effects model indicated significantly higher odds of post-TAVR PPM implantation for men (OR, 1.16; 95% CI, 1.04-1.28); for patients with baseline mobitz type-1 second-degree atrioventricular block (OR, 3.13; 95% CI, 1.64-5.93), left anterior hemiblock (OR, 1.43; 95% CI, 1.09-1.86), bifascicular block (OR, 2.59; 95% CI, 1.52-4.42), right bundle-branch block (OR, 2.48; 95% CI, 2.17-2.83), and for periprocedural atriorventricular block (OR, 4.17; 95% CI, 2.69-6.46). The mechanically expandable valves had 1.44 (95% CI, 1.18-1.76), while self-expandable valves had 1.93 (95% CI, 1.42-2.63) fold higher odds of PPM requirement compared with self-expandable and balloon-expandable valves, respectively. Conclusions Male sex, baseline atrioventricular conduction delays, intraprocedural atrioventricular block, and use of mechanically expandable and self-expanding prosthesis served as positive predictors of PPM implantation in patients undergoing TAVR.
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http://dx.doi.org/10.1161/JAHA.121.020906DOI Listing
July 2021

Comparative safety of percutaneous ventricular assist device and intra-aortic balloon pump in acute myocardial infarction-induced cardiogenic shock.

Open Heart 2021 Jun;8(1)

Cardiology, Detroit Medical Center, Detroit, Michigan, USA

Background: The relative safety of percutaneous left ventricular assist device (pVAD) and intra-aortic balloon pump (IABP) in patients with cardiogenic shock after acute myocardial infarction remain unknown.

Methods: Multiple databases were searched to identify articles comparing pVAD and IABP. An unadjusted OR was used to calculate hard clinical outcomes and mortality differences on a random effect model.

Results: Seven studies comprising 26 726 patients (1110 in the pVAD group and 25 616 in the IABP group) were included. The odds of all-cause mortality (OR 0.57, 95% CI 0.47 to 0.68, p=<0.00001) and need for revascularisation (OR 0.16, 95% CI, 0.07 to 0.38, p=<0.0001) were significantly reduced in patients receiving pVAD compared with IABP. The odds of stroke (OR 1.12, 95% CI 0.14 to 9.17, p=0.91), acute limb ischaemia (OR=2.48, 95% CI 0.39 to 15.66, p=0.33) and major bleeding (OR 0.36, 95% CI 0.01 to 25.39, p=0.64) were not significantly different between the two groups. A sensitivity analysis based on the exclusion of the study with the largest weight showed no difference in the mortality difference between the two mechanical circulatory support devices.

Conclusions: In patients with acute myocardial infarction complicated by cardiogenic shock, there is no significant difference in the adjusted risk of all-cause mortality, major bleeding, stroke and limb ischaemia between the devices. Randomised trials are warranted to investigate further the safety and efficacy of these devices in patients with cardiogenic shock.
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http://dx.doi.org/10.1136/openhrt-2021-001662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204163PMC
June 2021

Mutational Analysis of Myoclonin1 Gene in Pakistani Juvenile Myoclonic Epilepsy Patients.

Biomed Res Int 2021 20;2021:7509825. Epub 2021 Apr 20.

Cell and Molecular Biology Laboratory, Department of Zoology, University of the Punjab, Lahore 54590, Pakistan.

Juvenile myoclonic epilepsy (JME) is the most prevalent and genetically heterogeneous form of epilepsy and accounts for 10-30% of all the cases worldwide. Ef-hand domain- (c-terminal-) containing protein 1 () encodes for a nonion channel protein and mutations in this gene have been extensively reported in different populations to play a causative role in JME. Linkage between JME and 6p11-12 locus has already been confirmed in Mexican and Dutch families. A case-control study was conducted on Pakistani JME patients for the first time, aimed at finding out mutations that have been reported in different populations. For this purpose, 66 clinically diagnosed JME patients and 108 control subjects were included in the study. Blood samples were collected from all the participants, and DNA was isolated from the lymphocytes by the modified organic method. Total 3 exons of , harboring extensively reported mutations, were selected for genotypic analysis. We identified three heterozygous variants, R159W, V460A, P436P, and one insertion in the current study. V460A, an uncommon variant identified herein, has recently been reported in public databases in an unphenotyped American individual. This missense variant was found in 3 Pakistani JME patients from 2 unrelated families. However, analysis showed that V460A may possibly be a neutral variant. While the absence of a majority of previously reported mutations in our population suggests that most of the mutations of are confined to particular ethnicities and are not evenly distributed across the world. However, to imply the causation, the whole gene and larger number of JME patients should be screened in this understudied population.
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http://dx.doi.org/10.1155/2021/7509825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081613PMC
May 2021

Clinical outcomes of renal and liver transplant patients undergoing transcatheter aortic valve replacement: analysis of national inpatient sample database.

Expert Rev Cardiovasc Ther 2021 Apr 4;19(4):363-368. Epub 2021 Mar 4.

Department of Cardiology, Detroit Medical Center, Detroit, MI, USA.

The transcatheter aortic valve replacement (TAVR) has recently gained traction as a viable alternative to surgical aortic valve replacement (SAVR), but data on its safety and clinical outcomes in transplant patients are limited. We retrieved relevant demographic and clinical outcome data from the U.S. National Inpatient Sample (NIS) for the year 2012-2015. The clinical outcomes of TAVR in renal transplant (RT) and liver transplant (LT) were ascertained using an adjusted odds ratio (aOR) with a 95% confidence interval (CI) on Mantzel-Hensel test. A total of 62,399 TAVR patients were identified; 62,180 (99.6%) with no history of transplant, 219 (0.4%) with RT and 85 (0.1%) with LT. There was no significant difference in odds of in-hospital mortality (OR 0.61, 95% CI 0.25-1.5, p = 0.37), major cardiovascular, respiratory or neurological complications in patients with and without RT. Similarly, the odds of cardiac complications, renal and neurological complications between patients with and without LT were identical. Compared to non-transplant patients, TAVR appears to be associated with similar odds of major systemic complications or mortality in patients with a history of kidney or liver transplant.
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http://dx.doi.org/10.1080/14779072.2021.1892489DOI Listing
April 2021

Clinical outcomes of patients with diabetes mellitus and acute ST-elevation myocardial infarction following fibrinolytic therapy: a nationwide inpatient sample (NIS) database analysis.

Expert Rev Cardiovasc Ther 2021 Apr 26;19(4):357-362. Epub 2021 Feb 26.

Department of Cardiology, Detroit Medical Center, MI, USA.

The impact of diabetes mellitus (DM) on clinical outcomes of acute ST-segment elevation myocardial infarction (STEMI) following fibrinolytic therapy remains uncertain. We queried the National Inpatient Sample (NIS) for STEMI patients who received fibrinolytic therapy. Categorical and continuous variables were compared using the unadjusted odds ratio (uOR) and t-test analysis, respectively. A binary logistic regression model was used to control the outcomes for patient demographics, procedural characteristics, and baseline comorbidities. A total of 111,155 (no-DM 84,146, DM 27,009) were included. The unadjusted odds of in-hospital mortality (8.4% vs. 6.8%, uOR 1.25, 95% CI 1.19-1.31, P = <0.0001) and cardiogenic shock (7.7% vs. 6.2%, uOR 1.26, 95% CI 1.20-1.33, P = <0.0001) were significantly higher in patients with DM compared to those with no DM, respectively. The odds for major bleeding and cardiopulmonary arrest were significantly lower for in diabetes. The adjusted pooled estimates mirrored the unadjusted findings. Diabetic patients receiving fibrinolytic therapy for STEMI might have higher odds of all-cause mortality and cardiogenic shock compared to non-diabetic patients.
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http://dx.doi.org/10.1080/14779072.2021.1888716DOI Listing
April 2021

Association of interleukin-17 gene polymorphisms with the onset of Rheumatoid Arthritis.

Immunobiology 2021 01 3;226(1):152045. Epub 2020 Dec 3.

Cell and Molecular Biology Lab, Department of Zoology, University of the Punjab, Lahore, Pakistan.

Rheumatoid Arthritis (RA) is an autoimmune disorder where multiple cytokines including IL-17A and IL-17F produced by T helper cell 17 (Th17), contribute to its pathogenesis. By initiating inflammatory responses in joints Th17 act as pathogenic driver leading to bone and cartilage destruction in RA patients. Hence, the planned study was aimed to estimate IL-17 gene polymorphism association with RA susceptibility in Pakistani population. The present study included 100 subjects (50 RA patients and 50 healthy controls). Blood samples were taken and DNA was isolated for genotyping purpose. Chi square and Logistic regression analysis was performed to check the association of selected SNPs with RA. For rs2397084 and rs763780 polymorphism T allele acted as significant risk factor as compared to the reference C allele. TT vs. CC comparison in rs2397084 showed that T allele is a risk factor (OR 5.538; 95%Cl 1.757-17.458) in RA susceptibility. In case of rs763780 heterozygous CT (OR 10.80; 95% Cl 3.736-31.218) and homozygous mutant TT (OR 7.50; 95% Cl 2.360-23.831) genotypes proved to be a potential risk for RA patients. The significant differences in allelic and genotypic frequencies were observed for both SNPs. While for rs2275913 significantly varied frequency was observed only for dominant model of inheritance and non significant differences were seen at allelic level. Variation at all these three polymorphic sites substituted mutant amino acids leading to further functional changes in protein structure. Three polymorphic sites rs2275913, rs763780 and rs2397084 positioned on IL-17 gene were significantly strong factors in RA incidence among Pakistani population as they alter normal function of inflammatory cytokine IL-17.
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http://dx.doi.org/10.1016/j.imbio.2020.152045DOI Listing
January 2021

High-Fat Diet Induced Hedgehog Signaling Modifications during Chronic Kidney Damage.

Biomed Res Int 2020 27;2020:8073926. Epub 2020 Nov 27.

Cell & Molecular Biology Lab, Department of Zoology, University of the Punjab, Q-A-Campus, Lahore 54590, Pakistan.

Excessive consumption of dietary fats leads to the deposition of unnecessary metabolites and multiple organ damage. Lipids, important key regulators of Hedgehog signaling, are involved in triggering fibrotic chronic kidney disease. The present study encompasses the assessment of renal morphofunctional modifications and alteration of lipid metabolism influencing the changes in gene expression of hedgehog signaling pathway genes. Fifteen male of 200 ± 25 grams weight were equally divided into three groups: control (standard rat chow), D-1 (unsaturated high-fat diet) and D-2 (saturated high-fat diet). Animals were provided with respective diets and were followed for 16 weeks. Both HFD-fed groups did not show overall body weight gain as compared to the control. While significant downregulation of hedgehog pathway genes was found in fatty diet groups. In comparison with the control group, , , , and were downregulated after the consumption of both unsaturated and saturated fatty diets. and exhibit a similar downregulation in the D-1 group, but an upregulation was detected in the D-2 group. D-2 group also had an increased serum urea concentration as compared to the control ( = 0.0023). Furthermore, renal histopathology revealed tubular necrosis, glomerular edema, glomerular shrinkage, and hypocellularity. Collagen deposition in both HFD groups marks the extent of fibrosis summary figure. Extravagant intake of dietary fats impaired normal kidney functioning and morphofunctionally anomalous kidney triggers on Hh signaling in adult rats. These anomalies can be linked to an escalated risk of chronic kidney disease in adults strongly recommending the reduced uptake of fatty diets to prevent impaired metabolism and renal lipotoxicity.
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http://dx.doi.org/10.1155/2020/8073926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718043PMC
May 2021

Safety and efficacy of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis.

World J Cardiol 2020 Oct;12(10):501-512

Department of Cardiology, Thomas Jefferson University, Philadelphia, PA 19001, United States.

Background: The utility of novel oral soluble guanylate cyclase (sGC) stimulators (vericiguat and riociguat), in patients with reduced or preserved ejection fraction heart failure (HFrEF/HFpEF) is currently unclear.

Aim: To determine the efficacy and safety of sGC stimulators in HF patients.

Methods: Multiple databases were searched to identify relevant randomized controlled trials (RCTs). Data on the safety and efficacy of sGC stimulators were compared using relative risk ratio (RR) on a random effect model.

Results: Six RCTs, comprising 5604 patients (2801 in sGC stimulator group and 2803 placebo group) were included. The primary endpoint (a composite of cardiovascular mortality and first HF-related hospitalization) was significantly reduced in patients receiving sGC stimulators compared to placebo [RR 0.92, 95% confidence interval (CI): 0.85-0.99, = 0.02]. The incidence of total HF-related hospitalizations were also lower in sGC group (RR 0.91, 95%CI: 0.86-0.96, = 0.0009), however, sGC stimulators had no impact on all-cause mortality (RR 0.96, 95%CI: 0.86-1.07, = 0.45) or cardiovascular mortality (RR 0.94, 95%CI: 0.83-1.06, = 0.29). The overall safety endpoint (a composite of hypotension and syncope) was also similar between the two groups (RR 1.50, 95%CI: 0.93-2.42, = 0.10). By contrast, a stratified subgroup analysis adjusted by type of sGC stimulator and HF (vericiguat riociguat and HFrEF HFpEF) showed near identical rates for all safety and efficacy endpoints between the two groups at a mean follow-up of 19 wk. For the primary composite endpoint, the number needed to treat was 35, the number needed to harm was 44.

Conclusion: The use of vericiguat and riociguat in conjunction with standard HF therapy, shows no benefit in terms of decreasing HF-related hospitalizations or mortality.
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http://dx.doi.org/10.4330/wjc.v12.i10.501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596421PMC
October 2020

A giant coronary artery ectasia successfully managed conservatively.

J Community Hosp Intern Med Perspect 2020 Aug 2;10(4):343-345. Epub 2020 Aug 2.

Internal Medicine, Abington Hospital- Jefferson Health, Abington, PA, USA.

Coronary artery aneurysms (CAA) is a rare condition characterized by abnormal dilatation of the coronary arteries. We present a case of a 77-year-old gentleman who presented with atypical chest pain and was found to have elevated cardiac enzymes. He underwent diagnostic left heart catheterization which revealed left main CAA and significant left circumflex stenosis. The patient was administered medical therapy and was discharged home in a stable condition. The purpose of this report is to highlight a rare case of a large CAA which was successfully managed conservatively.
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http://dx.doi.org/10.1080/20009666.2020.1773710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427445PMC
August 2020

Complications of leadless vs conventional (lead) artificial pacemakers - a retrospective review.

J Community Hosp Intern Med Perspect 2020 Aug 2;10(4):328-333. Epub 2020 Aug 2.

Detroit Medical Center, Wayne State University, Detroit, Michigan, USA.

Background: Leadless pacemakers (LPM) are introduced in cardiovascular market with a goal to avoid lead- and pocket-associated complications due to conventional artificial pacemakers (CPM). The comparison of LPM and CPM complications is not well studied at a case by case level.

Methods: Comprehensive literature was searched on multiple databases performed from inception to December 2019 and revealed 204 cases that received LPM with a comparison of CPM. The data of complications were extracted, screened by independent authors and analyzed using IBM SPSS Statistics for Windows, Version 22.0 (Armonk, NY: IBM Corp.).

Results: The complications of CPM were high in comparison to LPM in terms of electrode dislodgement (56% vs 7% of cases, p-value < .0001), pocket site infection rate (16% vs 3.4%, p-value = 0.02), and a lead fracture rate (8% vs 0%, p-value = 0.04). LPMs had a statistically non-significant two-times high risk of pericardial effusion (8%) compared to CPMs (4%) with a p-value = 0.8.

Conclusion: LPMs appear to have a better safety profile than CPMs. There was a low pocket site and lead-related infections in LPM as compared to CPM. However, LPM can have twice the risk of pericardial effusion than CPMs, but this was not statistically significant.
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http://dx.doi.org/10.1080/20009666.2020.1786901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427453PMC
August 2020

A rare association of Takotsubo cardiomyopathy with neuroleptic malignant syndrome.

J Community Hosp Intern Med Perspect 2020 May 21;10(2):133-137. Epub 2020 May 21.

Saint Mary Medical Center, Philadelphia, PA, USA.

Neuroleptic malignant syndrome is a potentially fatal neurological condition secondary to antipsychotic medication. It is characterized by distinctive clinical findings and autonomic disturbances. NMS has not been associated with Takotsubo cardiomyopathy (TCM). TCM is an abnormal response to physiological stressors resulting from the autonomic abnormalities which at times can mimic myocardial infarction (MI). We present a unique case of a 54-year-old female with bipolar disease presenting with lithium and haloperidol-induced NMS complicated by TCM. The purpose of this case is to make clinicians aware of this rare association.
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http://dx.doi.org/10.1080/20009666.2020.1742522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425628PMC
May 2020

Safety and Efficacy of Hydroxychloroquine in COVID-19: A Systematic Review and Meta-Analysis.

J Clin Med Res 2020 Aug 4;12(8):483-491. Epub 2020 Jul 4.

Thomas Jefferson University, Philadelphia, PA, USA.

Background: During the initial phases of the coronavirus disease 2019 (COVID-19) epidemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ); however, recently, the Centers for Disease Control and Prevention (CDC) has recommended against routine use of HCQ outside of study protocols citing possible adverse outcomes.

Methods: Multiple databases were searched to identify articles on COVID-19. An unadjusted odds ratio (OR) was used to calculate the safety and efficacy of HCQ on a random effect model.

Results: Twelve studies comprising 3,912 patients (HCQ 2,512 and control 1400) were included. The odds of all-cause mortality (OR: 2.23, 95% confidence interval (CI): 1.58 - 3.13, P value < 0.00001) were significantly higher in patients on HCQ compared to patients on control agent. The response to therapy assessed by negative repeat polymerase chain reaction (PCR) (OR: 1.83, 95% CI: 0.50 - 6.75, P = 0.36), radiological resolution (OR: 1.98, 95% CI: 0.47 - 8.36, P value = 0.36) and the need for invasive mechanical ventilation (IMV) (OR: 1.21, 95% CI: 0.34 - 4.33, P value = 0.76) were identical between the two groups. Overall, four times higher odds of net adverse events (NAEs) were observed in the HCQ group (OR: 4.59, 95% CI 1.73 - 12.20, P value = 0.02). The measures for individual safety endpoints were also numerically lower in the control arm; however, none of these values reached the level of statistical significance.

Conclusions: HCQ might offer no benefits in terms of decreasing the viral load and radiological improvement in patients with COVID-19. HCQ appears to be associated with higher odds of all-cause mortality and NAEs.
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http://dx.doi.org/10.14740/jocmr4233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430873PMC
August 2020

Percutaneous Intervention or Bypass Graft for Left Main Coronary Artery Disease? A Systematic Review and Meta-Analysis.

J Interv Cardiol 2020 26;2020:4081642. Epub 2020 Jul 26.

Thomas Jefferson University, Philadelphia, PA, USA.

Background: The safety and efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) for stable left main coronary artery disease (LMCAD) remains controversial.

Methods: Digital databases were searched to compare the major adverse cardiovascular and cerebrovascular events (MACCE) and its components. A random effect model was used to compute an unadjusted odds ratio (OR).

Results: A total of 43 studies (37 observational and 6 RCTs) consisting of 29,187 patients (PCI 13,709 and CABG 15,478) were identified. The 30-day rate of MACCE (OR, 0.56; 95% CI, 0.42-0.76;  = 0.0002) and all-cause mortality (OR, 0.52; 95% CI, 0.30-0.91;  = 0.02) was significantly lower in the PCI group. There was no significant difference in the rate of myocardial infarction (MI) ( = 0.17) and revascularization ( = 0.12). At 5 years, CABG was favored due to a significantly lower rate of MACCE (OR, 1.67; 95% CI, 1.18-2.36;  = <0.04), MI (OR, 1.67; 95% CI, 1.35-2.06;  = <0.00001), and revascularization (OR, 2.80; 95% CI, 2.18-3.60;  = <0.00001), respectively. PCI was associated with a lower overall rate of a stroke, while the risk of all-cause mortality was not significantly different between the two groups at 1- ( = 0.75), 5- ( = 0.72), and 10-years ( = 0.20). The Kaplan-Meier curve reconstruction revealed substantial variations over time; the 5-year incidence of MACCE was 38% with CABG, significantly lower than 45% with PCI ( = <0.00001).

Conclusion: PCI might offer early safety advantages, while CABG provides greater durability in terms of lower long-term risk of ischemic events. There appears to be an equivalent risk for all-cause mortality.
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http://dx.doi.org/10.1155/2020/4081642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399756PMC
January 2021

Comparative accuracy of non-invasive imaging versus right heart catheterization for the diagnosis of pulmonary hypertension: A systematic review and meta-analysis.

Int J Cardiol Heart Vasc 2020 Aug 1;29:100568. Epub 2020 Jul 1.

Thomas Jefferson University, PA, United States.

Background: Right heart catheterization (RHC) is the gold-standard in the diagnosis of pulmonary hypertension (PH) but at the cost of procedure-related complications. We sought to determine the comparative accuracy of RHC versus non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and transthoracic echocardiography (TTE).

Methods: Pulmonary hypertension was defined as a mean pulmonary artery pressure (mPAP) of>20 mmHg. Multiple databases were queried for relevant articles. Raw data were pooled using a bivariate model to calculate the measures of diagnostic accuracy and to estimate Hierarchical Summary Receiver Operating Characteristic (HSROC) on Stata 13.

Results: A total of 51 studies with a total patient population of 3947 were selected. The pooled sensitivity and specificity of MRI for diagnosing PH was 0.92(95% confidence interval (CI) 0.88-0.96) and 0.86 (95% CI, 0.77-0.95), respectively. The net sensitivities for CT scan and TTE were 0.79 (95% CI 0.72-0.89) and 0.85 (95% CI 0.83-0.91), respectively. The overall specificity was 0.82 (0.76-0.92) for the CT scan and 0.71 (95% CI 0.61-0.84) for TTE. The diagnostic odds ratio (DOR) for MRI was 124 (95% CI 36-433) compared to 30 (95% CI 11-78) and 24 (95% 11-38) for CT scan and TTE, respectively. Chi-squared (2) test showed moderate heterogeneity on the test for equality of sensitivities and specificities.

Conclusions: MRI has the highest sensitivity and specificity compared to CT and TTE. MRI can potentially serve as a surrogate technique to RHC for the diagnosis of PH.
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http://dx.doi.org/10.1016/j.ijcha.2020.100568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334462PMC
August 2020

Cost-effectiveness and diagnostic accuracy of telemedicine in macular disease and diabetic retinopathy: A systematic review and meta-analysis.

Medicine (Baltimore) 2020 Jun;99(25):e20306

Internal Medicine, Griffin Hospital, CT, USA.

Objective: To determine cost-effectiveness and the diagnostic accuracy of teleophthalmology (TO) in the detection of macular edema (ME) and various grades of diabetic retinopathy (DR).

Methods: MEDLINE, EMBASE, and Cochrane databases were searched for TO, ME, and DR on May 25, 2016. The search was updated on April 2, 2019. Pooled sensitivity and specificity for ME and various grades of DR were determined using Meta-Disc software. A systematic review of the articles discussing the cost-effectiveness of TO screening was also performed.

Results: Thirty-three articles on the diagnostic accuracy and 28 articles on the cost-effectiveness were selected.

Conclusions: Telescreening is moderately sensitive but very specific for the diagnosis of diabetic retinopathy. Non-mydriatic Teleretinal screening services are cost-effective, decrease clinics workload, and increase patient compliance if provided free of cost in remote low socioeconomic regions.
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http://dx.doi.org/10.1097/MD.0000000000020306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310976PMC
June 2020

Diagnostic Accuracy of Cardiac Magnetic Resonance Versus Fractional Flow Reserve: A Systematic Review and Meta-Analysis.

Cardiol Res 2020 Jun 3;11(3):145-154. Epub 2020 May 3.

St. Mary Medical Center, Langhorne, PA, USA.

Background: Fractional flow reserve (FFR) is considered the gold standard for diagnosis of coronary artery disease (CAD). Stress Cardiac magnetic resonance (SCMR) has been recently gaining traction as a non-invasive alternative to FFR.

Methods: Studies comparing the diagnostic accuracy of SCMR versus FFR were identified and analyzed using Review Manager (RevMan) 5.3 and Stata software.

Results: A total of 28 studies, comprising 2,387 patients, were included. The pooled sensitivity and specificity for SCMR were 86% and 86% at the patient level, and 82% and 88% at the vessel level, respectively. When the patient-level data were stratified based on the FFR thresholds, higher sensitivity and specificity (both 90%) were noted with the higher cutoff (0.75) and lower cutoff (0.8), respectively. At the vessel level, sensitivity and specificity at the lower FFR threshold were significantly higher at 88% and 89%, compared to the corresponding values for higher cutoff at 0.75. Similarly, meta-regression analysis of SCMR at higher (3T) resolution showed a higher sensitivity of 87% at the patient level and higher specificity of 90% at the vessel level. The highest sensitivity and specificity of SCMR (92% and 94%, respectively) were noted in studies with CAD prevalence greater than 60%.

Conclusions: SCMR has high diagnostic accuracy for CAD comparable to FFR at a spatial resolution of 3T and an FFR cut-off of 0.80. An increase in CAD prevalence further improved the specificity of SCMR.
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http://dx.doi.org/10.14740/cr1028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239594PMC
June 2020

Outcomes of open mitral valve replacement versus Transcatheter mitral valve repair; insight from the National Inpatient Sample Database.

Int J Cardiol Heart Vasc 2020 Jun 28;28:100540. Epub 2020 May 28.

Detroit Medical Center, DMC Heart Hospital, Detroit, MI, USA.

Background: Transcatheter mitral valve repair and replacement (TMVR) is a minimally invasive alternative to conventional open-heart mitral valve replacement (OMVR). The present study aims to compare the burden, demographics, cost, and complications of TMVR and OMVR.

Methods: The United States National Inpatient Sample (US-NIS) for the year 2017 was queried to identify all cases of TMVR and OMVR. Categorical and continuous data were analyzed using Pearson chi-square and independent -test analysis, respectively. An adjusted odds ratio (aOR) based on the ordinal logistic regression (OLR) model was calculated to determine the association between outcome variables.

Results: Of 19,580 patients, 18,460 (94%) underwent OMVR and 1120 (6%) TMVR. Mean ages of patients were 63 ± 14 years (OMVR) and 67 ± 13 years (TMVR). Both cohorts were predominantly Caucasian (73% OMVR vs. 74.0% TMVR). The patients who underwent TMVR were more likely to belong to a household with an income in the highest quartile (26.1% vs. 22.0% for OMVR) versus the lowest quartile (22.1% vs. 27.8%). The average number of days from admission to TMVR was less compared to OMVR (2.63 days vs. 3.02 days, p = 0.015). In-hospital length of stay (LOS) was significantly lower for TMVR compared to OMVR (11.56 vs. 14.01 days, p=<0.0001). Adjusted in-hospital mortality taking into account comorbidities showed no significant difference between the two groups (OR 1.2, 0.93-1.68, p = 0.15).

Conclusion: Patients undergoing TMVR were older and more financially affluent. TMVR was more costly but was associated with a shorter hospital stay and similar mortality to OMVR.
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http://dx.doi.org/10.1016/j.ijcha.2020.100540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262433PMC
June 2020

Spontaneous Coronary Artery Dissection Secondary to Rheumatological Diseases: A Comprehensive Review.

Cureus 2019 Jul 24;11(7):e5231. Epub 2019 Jul 24.

Cardiology, Saint Mary Medical Center, Philadelphia, USA.

Spontaneous coronary artery dissection (SCAD) is a life-threatening condition and multiple conditions have been associated with this entity. This study aims to further investigate and characterize the association of the underlying rheumatological disease with SCAD. A comprehensive literature search on four databases was performed using different Medical Subject Headings (MeSH) and all articles on SCAD in association with rheumatological diseases were identified. The analysis was performed using the Statistical Package for Social Sciences (SPSS), v22 (IBM SPSS Statistics, Armonk, NY). Ten articles of SCAD secondary to rheumatological reasons were identified. The majority of presentations were associated with systemic lupus erythematosus (SLE). Most patients presented with a non-ST-elevation myocardial infarction (NSTEMI) involving the left main coronary vessel. The majority of them were successfully managed with stenting. Mortality was less than 20% with prompt identification and management of the SCAD. SLE was the most commonly reported rheumatological condition associated with SCAD. Prompt diagnosis and management of SCAD in such patients can be life-saving.
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http://dx.doi.org/10.7759/cureus.5231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6758995PMC
July 2019

Acute Mesenteric Tuberculous Lymphadenitis: A Comparative Analysis of Twenty-one Cases.

Cureus 2019 Apr 13;11(4):e4454. Epub 2019 Apr 13.

Internal Medicine, Abington Hospital-Jefferson Health, Abington, USA.

Tuberculosis (TB) remains a major public health concern. Atypical extrapulmonary presentations of this infection may significantly delay its diagnosis and management. Tuberculous lymphadenitis (TL) is an extrapulmonary manifestation of a Mycobacterium tuberculosis infection. It is characterized by necrotizing mycobacterial infection of the lymph nodes. The clinical presentation of this disease ranges from fever and malaise to cervical lymphadenopathy and fistula formation. Herein, we present a comprehensive review of the previously reported cases of mesenteric lymphadenitis. The purpose of this study is to acquaint physicians to identify this disease in a timely manner. Furthermore, this review also highlights the rare presentation and management of TL.
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http://dx.doi.org/10.7759/cureus.4454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561514PMC
April 2019

Methotrexate and doxycycline interaction: a rare cause of pancytopenia.

BMJ Case Rep 2019 May 31;12(5). Epub 2019 May 31.

Abington Hospital - Jefferson Health, Abington, Pennsylvania, USA.

Methotrexate (MTX) was originally formulated as one of the first antitumour drugs due to its ability to alter folate metabolism, which renders it to be an antiproliferative agent. Classically, the higher dosage is administered via parenteral route, in a cyclical fashion, to achieve antitumour effects. Patients on high doses of MTX are prone to develop rare complications of myelosuppression and pancytopenia, in a dose-dependent fashion, secondary to altered folate metabolism. Herein, we present a unique case of rheumatoid arthritis presented with pancytopenia due to low-dose MTX and doxycycline drug interaction. We also report the successful management of pancytopenia and oral ulcers with combination therapy of leucovorin and granulocyte colony-stimulating factor.
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http://dx.doi.org/10.1136/bcr-2019-229296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557379PMC
May 2019

Diagnosis and Management of Isolated Superior Mesenteric Artery Dissection: A Systematic Review and Meta-Analysis.

Korean Circ J 2019 May;49(5):400-418

Division of Cardiology, St. Mary Medical Center, Langhorne, PA, USA.

The objective of this study was to analyze the three different management modalities for isolated superior mesenteric artery (SMA) dissection. We did a comprehensive literature search and found 703 articles on the initial search, out of which 111 articles consisting of 145 patients were selected for analysis. The mean age was 55.7 years (standard deviation,9.7;33-85) and 80.6% were male. These patients were managed conservatively (41.3%), endovascularly (28.1%) or surgically (30%). The median follow-up was 10 months (interquartile range [IQR], 4-18 months), 12 months (IQR, 6-19 months) and 14 months (IQR, 6-20 months) respectively. Contrast-enhanced computed tomography (CT) was the most commonly used diagnostic tool in the conservative group (43.8%), while conventional CT scan was the most widely used in endovascular (58.1%) and surgical group (50%). 17% percent of the conservative group had SMA angiography for diagnosis, while this was less than 3% in the other groups. Of these patients, 96.7%, 97.4%, and 100.0% recovered successfully in the conservative, endovascular, and surgical groups respectively. There was no significant difference in the mortality between the three groups (Pearson χ²=0.482). This suggests a conservative and endovascular approach could be used in most patients, which can reduce costs and surgery-related morbidity and mortality. Surgical management should be reserved for cases having infarction or widespread bowel ischemia and in cases where other treatment modalities fail.
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http://dx.doi.org/10.4070/kcj.2018.0429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511528PMC
May 2019

Vitamin D Receptor Gene Polymorphism: An Important Predictor of Arthritis Development.

Biomed Res Int 2019 18;2019:8326246. Epub 2019 Mar 18.

Cell and Molecular Biology Lab, Department of Zoology, University of the Punjab, Quaid-i-Azam Campus, Lahore 54590, Pakistan.

Vitamin D is an anti-inflammatory molecule and has a role in prevention of arthritis development. Biologically active form 1, 25(OH)D3 of vitamin D can only exert its action after binding its definite vitamin D receptor encoded by VDR gene. VDR gene polymorphism leads to dysfunctioning of 1, 25(OH)D ultimately disease onset. The purpose of current study was to evaluate the effect of vitamin D level and VDR gene polymorphism on rheumatoid arthritis and osteoarthritis. Blood samples were collected from case and control after taking written consent. Serum was separated and vitamin D level as determined from each sample by ELISA. DNA was extracted from each blood sample and amplified by using gene specific primers. Genotyping was performed by Sangers sequencing and PCR-RFLP technique. It was found that vitamin D level was not significantly different among patients and controls. The rs10735810, rs1544410, rs7975232, and rs731236 were associated with the onset of arthritis at both allelic and genotypic level (p < 0.01). Nucleotide change on rs10735810 site leads to change of tryptophan with arginine. The frequencies of haplotype CGAT, CGGA, CGGT, CTAA, CTAT, TGAA, TGAT, TGGA, and TTGA were higher in patients and act as risk factors of RA onset, whereas haplotypes CGAT, CGAT, CGGT, CTGA, TGAT, TGGA, TTAA, and TTGA were associated with OA onset. In conclusion, serum vitamin D level may be normal among arthritis patients but polymorphism on VDR gene restricts vitamin D to perform its anti-inflammatory function by altering the 1, 25(OH)2 D3 binding sites.
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http://dx.doi.org/10.1155/2019/8326246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442488PMC
August 2019

Acupuncture-Related Cardiac Complications: A Systematic Review.

J Invasive Cardiol 2019 04;31(4):E69-E72

St. Mary Medical Center, 1203 Langhorne-Newtown Road, Suite 320, Langhorne, PA 19047 USA.

Background: The objective of this study is to review acupuncture-related cardiac complications, such as infective endocarditis (IE), cardiac tamponade (CT), pericarditis, and cardiac rupture, as there is no known reported literature to determine the burden of cardiac adverse events due to acupuncture.

Methods: Structured computerized databases were searched using the special Medical Subject Heading (MeSH). Manual search using the references of relevant articles was also performed.

Results: A total of 133 articles were initially retrieved, but careful reading resulted in only 30 cases of relevant cardiac adverse events. There were 8 articles of infective complications (mostly IE), while 22 articles of CT have been reported to date. The diagnoses were made with echocardiography and patients were treated with intravenous antibiotics. The source of the infection was mostly localized to acupuncture needle prick sites, such as earlobes and legs. Mortality rate for post-acupuncture CT was not significantly higher than infective cardiac complication (Pearson's Chi-square = 0.559; likelihood ratio = 0.553). However, the weighted percentage of death was about 80% in CT vs only 20% mortality for infective cardiac complications. On the other hand, CT was the most common presentation when the needle pricks were close to the heart, and had a clinical presentation of hypotension and venous distention.

Conclusions: Although the universally reported complications of acupuncture are low, and the procedure itself has been deemed low risk in acupuncture-related literature, these cardiac complications are alarming. To avoid these potentially catastrophic consequences, more education needs to be done for adopting safer techniques.
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April 2019

Gitelman Syndrome: A Rare Cause of Seizure Disorder and a Systematic Review.

Case Rep Med 2019 5;2019:4204907. Epub 2019 Feb 5.

Resident Physician, Abington Hospital-Jefferson Health, Abington, PA, USA.

Gitelman syndrome is one of the few inherited causes of metabolic alkalosis due to salt losing tubulopathy. It is caused by tubular defects at the level of distal convoluted tubules, mimicking a thiazide-like tumor. It usually presents in late childhood or in teenage as nonspecific weakness, fatigability, polyuria, and polydipsia but very rarely with seizures. It is classically associated with hypokalemia, hypomagnesemia, hypocalciuria, hyperreninemia, and hyperaldosteronism. However, less frequently, it can present with normal magnesium levels. It is even rarer to find normomagnesemic patients of GS who develop seizures as the main complication since hypomagnesemia is considered the principal etiology of abnormal foci of seizure-related brain activity in GS cases. Interestingly, patients with GS are oftentimes diagnosed during pregnancy when the classic electrolyte pattern consistent with GS is noticed. Our case presents GS with normal serum magnesium in a patient, with seizures being the main clinical presentation. We also did a comprehensive literature review of 122 reported cases to show the prevalence of normal magnesium in GS cases and an overview of clinical and biochemical variability in GS. We suggest that further studies and in-depth analysis are required to understand the pathophysiology of seizures in GS patients with both normal and low magnesium levels.
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http://dx.doi.org/10.1155/2019/4204907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379858PMC
February 2019

Sudden death due to pulmonary embolism after minor ankle surgery.

BMJ Case Rep 2019 Mar 6;12(3). Epub 2019 Mar 6.

Internal Medicine, Abington Jefferson Health, Abington, Pennsylvania, USA.

Venous thromboembolism prophylaxis guidelines are clear for major orthopaedic surgeries, but data regarding ankle surgery are insufficient. Death from pulmonary embolism (PE) after ankle surgery is rare with the frequency of less than 0.037%. We present a case of a fatal PE after ankle surgery to raise awareness about this rare but potentially fatal complication. Our patient had a left ankle fracture status postsurgical fixation and was discharged without venous thromboembolism (VTE) prophylaxis. Twenty days later, she presented with a sudden onset of dyspnoea and palpitations and was diagnosed to have extensive right-sided PE. Intravenous heparin and thrombolytics were given, but she had multiple pulseless electrical activity arrests, developed disseminated intravascular coagulation and died. Our case depicts an unusual complication of ankle surgery and highlights the importance of considering VTE as one of the complications. Medical personnel should evaluate the need for VTE prophylaxis after ankle surgery on a case to case basis.
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http://dx.doi.org/10.1136/bcr-2018-227649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424277PMC
March 2019

An Esophagogram or Tracheobronchogram? A Review of Barium Sulfate Aspiration.

J Investig Med High Impact Case Rep 2018 Jan-Dec;6:2324709618802872. Epub 2018 Oct 4.

State University of New York Downstate Medical Center, Brooklyn, NY, USA.

The barium swallow is an important radiological investigation used for the diagnosis of upper gastrointestinal anatomical disorders like esophageal cancer, diverticulum, achalasia, foreign body, among others. Generally, it is believed to be a safe technique with rare complications, but few cases of barium sulfate aspiration have been reported in the literature with multiple complications. We are reporting a case of an elderly male who underwent esophagogram for the workup of chronic dysphagia, aspirated barium sulfate, and went into respiratory failure and circulatory shock several hours later. Moreover, we also did a systematic literature search and reviewed all available articles on aspiration of barium sulfate and its potential complications. We focused on predisposing factors for aspiration, clinical presentation, complications after aspiration, and prognosis with the aim to better understand and manage this condition.
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http://dx.doi.org/10.1177/2324709618802872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172932PMC
October 2018

A novel single nucleotide polymorphism in exon 3 of MYOC enhances the risk of glaucoma.

PLoS One 2018 9;13(4):e0195157. Epub 2018 Apr 9.

Department of Zoology, Quaid-e-Azam Campus, University of the Punjab, Lahore, Pakistan.

Genetic polymorphismsof MYOCalter the myocilin protein,which leads to disruption of thenormal regulation of intraocular pressure (IOP) that ultimately causes glaucoma.Theaim of the present study was to identify the polymorphism in exon 3 of the MYOC gene of theglaucoma patients in Lahore, Pakistan. We conducted a case-control study with 100 patients and 100 controls subjects. We extracted DNA from blood samples,amplified the target DNA fragmentby PCR, and identifiedpolymorphisms through sequencing. We observed that the allelic and genotypic frequencies of rs74315341 and rs879255525 were associated with glaucoma in our patient population. The polymorphism atrs74315341 led to the substitutionof serine for arginine,whereas the polymorphism at rs879255525 led to the substitution ofasparagine for lysine. The haplotype TGAAGCCATTTC was associated with disease onset, whereas the haplotype GGAAGCCATTTC was protective against disease development. In conclusion, weidentified MYOC gene polymorphisms in susceptible regions that were associated withglaucoma onset among the Lahore patient population.This is the first report to identify a novel mutation in rs879255525 in exon 3 of the MYOC genethat is associated withglaucoma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890997PMC
July 2018

Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis.

Int J Genomics 2017 3;2017:4171254. Epub 2017 Dec 3.

Department of Zoology, G.C. University, Punjab, Lahore 54000, Pakistan.

Background: The vitamin D receptor () gene regulates insulin secretion from the pancreas and acts as a mediator of the immune response through vitamin D. Polymorphism in causes alterations in the functioning of vitamin D, leading to type 1 diabetes (T1D) predisposition. The aim of the present study was to determine gene polymorphism in association with T1D in Pakistanis.

Methods: The association was evaluated by selecting rs2228570 (), rs7975232 (Ι), and rs731236 (Ι) polymorphic sites in 102 patients and 100 controls. Genotypes were identified by DNA sequencing and PCR-RFLP.

Results: The allelic and genotypic frequencies of and I were significantly associated with T1D ( < 0.001) development. At the Ι site, tryptophan was replaced with arginine due to polymorphism. A novel SNP (GeneBank acc number KT280406) was identified through the sequencing of intron 8, 62 bp downstream from the I polymorphic site, and significantly associated with T1D development. The did not depict any association with T1D at the allelic or genotypic level ( > 0.05). CCGC, CCGG, CCTC, and CCTG haplotypes were significantly associated with disease development ( < 0.05). However, CTGG haplotype was protective towards T1D ( < 0.01).

Conclusion: polymorphisms were identified as susceptible regions for T1D development in the Pakistani population.
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http://dx.doi.org/10.1155/2017/4171254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733195PMC
December 2017

IL-32θ: a recently identified anti-inflammatory variant of IL-32 and its preventive role in various disorders and tumor suppressor activity.

Am J Transl Res 2017 15;9(11):4726-4737. Epub 2017 Nov 15.

Department of Zoology, University of The Punjab, Q-A CampusLahore, 54590, Pakistan.

Interleukin-32 theta (IL-32θ) is newly identified isoform of IL-32 which plays a vital role in inflammatory responses. Like IL-32α and IL-32β, IL-32θ isoform acts as an intracellular inflammatory modulator. It results in reduction of IL-1β production by attenuating the expression of PU.1 and inhibition of monocytes differentiation into macrophages. IL-32θ hinders TNF-α expression by inhibiting p38 MAPK and inhibitor of κB (IκB) as well. It also reserved STAT3-ZEB1 pathway leading to the inhibition of epithelial-mesenchymal transition (EMT) and stemness. Hence, it can be concluded that IL-32θ is an anti-inflammatory cytokine that can act as a tumor suppressor and can play vital role in colon cancer therapies. IL-32θ also plays a crucial role in immune system responses and cellular differentiation during disease pathogenesis. To our best knowledge this is the first ever review to condense the importance, precise mode of action in disease progression and latent remedial implications of IL-32θ in several inflammatory disorders.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714761PMC
November 2017
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